Dr. Michael Kohanski is an assistant professor in the Department of Otorhinolaryngology ? Head and Neck Surgery at the Perelman School of Medicine at The University of Pennsylvania. His clinical practice is focused on the medical and surgical management of inflammatory sinus and nasal disorders to improve the upper respiratory health of his patients. Dr. Kohanski's recent research efforts led to the finding that rare taste receptor expressing cells, solitary chemosensory cells (SCCs), are significantly enriched in inflammatory sinus polyps. This work established a connection between chronic rhinosinusitis (CRS) seen in humans to the important finding that tuft cells (analogous chemosensory cells in the intestine) are crucial for regulating Type 2 immunity. With the support of this award, Dr. Kohanski will develop expertise in mucosal immunology, epithelial physiology and bioinformatics to study solitary chemosensory cell regulation of airway inflammation and repair. Dr. Kohanski will augment his fund of knowledge through course work on immunology, epithelial physiology and bioinformatics. He will acquire new research skills with focused mentoring and training from a multidisciplinary group of experienced researchers at the University of Pennsylvania with expertise in epithelial taste receptor biology, Type 2 inflammation and epithelial cell physiology and repair as well as bioinformatics. This proposal focuses on identifying and characterizing taste-specific or inflammatory-specific inputs that stimulate SCC differentiation as well as understanding the mechanisms by which solitary chemosensory cells can amplify inflammatory and innate mucosal responses. This is a novel area of research with little work to date characterizing the role or function of chemosensory cells directly in human upper respiratory inflammatory diseases such as CRS with nasal polyps.
In Aim 1 a, Dr. Kohanski will characterize SCC abundance and SCC- specific gene expression directly in chronic rhinosinusitis with nasal polyps and determine if SCC abundance correlates with phenotypic markers of airway inflammation in a cohort of patients with CRS.
In Aim 1 b, he will determine if taste or inflammatory input stimulate differentiation of human SCCs and if there are distinct human SCC subtypes.
In Aim 1 c, the PI will leverage initial RNAseq results to further study the mechanisms of SCC differentiation and epithelial repair.
In Aim 2, Dr. Kohanski will test the hypothesis that SCC-mediated epithelial signaling occurs through two-pore potassium channels.
In Aim 2 a, he will utilize Ussing chambers to determine if inflammation or SCC abundance affects K2P channel function.
In Aim 2 b, he will use a house dust mite model of inflammation with mouse strains deficient in two-pore potassium channels or SCC taste transduction to determine if inflammation amplifies the ability of SCCs to regulate epithelial defensin release. Progression through these experiments coupled with expert mentorship and coursework will provide Dr. Kohanski with the foundation to become an independent investigator with a focus on epithelial chemosensory cell function and the resultant impact on the mucosal immune response and inflammatory airway disease.
Chronic rhinosinusitis affects up to 16% of the population in the United States and is among the most common reasons people seek medical attention. Solitary chemosensory cells (SCCs), akin to type II taste cells in the tongue (responsible for taste transduction) and tuft cells in the mouse gut (responsible for local inflammation) are enriched in the sinus epithelium in those with chronic rhinosinusitis with nasal polyps, however, little is known about their role in human mucosal inflammatory diseases. This proposal will characterize and identify taste and inflammatory pathways related to SCC differentiation and expansion in chronic rhinosinusitis and explore how SCC signaling through epithelial ion channels affects mucosal immune function, which may reveal novel therapeutic targets for the treatment of chronic rhinosinusitis.
